A FRET-Based Ratiometric H2S Sensor for Sensitive Optical Molecular Imaging in Second Near-Infrared Window.

Second near-infrared (NIR-II) window optical molecular imaging kicks off a new revolution in high-quality imaging in vivo, but always suffers from the hurdles of inevitable tissue autofluorescence background and NIR-II probe development. Here, we prepare a Förster resonance energy transfer-based ratiometric NIR-II window hydrogen sulfide (H2S) sensor through the combination of an H2S-responsive NIR-II cyanine dye (acceptor, LET-1055) and an H2S-inert rhodamine hybrid polymethine dye (donor, Rh930). This sensor not only exhibits high sensitivity and selectivity, but also shows rapid reaction kinetics (~20 min) and relatively low limit of detection (~96 nM) toward H2S, allowing in vivo ratiometric NIR-II fluorescence imaging of orthotopic liver and colon tumors and visualization of the drug-induced hepatic H2S fluctuations. Our findings provide the potential for advancing the feasibility of NIR-II activity-based sensing for in vivo clinical diagnosis.

In Vivo Near-Infrared Fluorescence/Ratiometric Photoacoustic Duplex Imaging of Lung Cancer-Specific hNQO1.

Overexpressing human NAD(P)H:quinone oxidoreductase 1 (hNQO1) in lung cancer tissues is deemed to be an attractive biomarker, which is directly connected to cancerous pathological processes. Monitoring of hNQO1 activity is crucial to early diagnosis and prognosis of lung cancer. In this study, an activatable hemi-cyanine dye-based probe (denoted as the LET-10 probe) was synthesized for near-infrared fluorescence (NIRF) and ratiometric photoacoustic (RPA) imaging of hNQO1. LET-10 can realize the NIRF and PA signal opening in the presence of hNQO1. Taking the octabutoxy naphthalocyanine in the LET-10 probe as a built-in reference signal, the LET-10 probe further demonstrated a double-signal self-calibration process for RPA imaging. Finally, the LET-10 probe was successfully applied for NIRF/RPA duplex imaging in the hNQO1-positive A549 lung cancer model, which suggests that the LET-10 probe is a promising tool for in vivo hNQO1 detection, especially for lung cancer diagnosis.

Enzyme-Engineered Conjugated Polymer Nanoplatform for Activatable Companion Diagnostics and Multistage Augmented Synergistic Therapy.

Companion diagnostics (CDx) provides critical information for precision medicine. However, current CDx is mostly limited to in vitro tests, which cannot accurately evaluate the disease progression and treatment response in real time. To overcome this challenge, herein a glucose oxidase (GOx)-engineered conjugated polymer (polyaniline, PANI) nanoplatform (denoted as PANITG) is reported for activatable imaging-based CDx and multistage augmented photothermal/starvation synergistic therapy. PANITG comprises a pH-activatable conjugated polymer as a photothermal convertor and photoacoustic (PA) emitter, a GOx as a cancer starvation inducer as well as a H2 O2 and acid producer, and a H2 O2 -cleavable linker as a "switch" for GOx activity. The in vivo PA imaging and photothermal therapy abilities are activated by acidic tumor microenvironment and self-augmented by the reaction between GOx and glucose. Meanwhile, the photothermal effect will enhance the GOx activity in turn. Such multistage augmentation of the therapeutic effects will facilitate effective cancer management. In addition, the in vivo PA imaging with PANITG reveals the tumor pH level which is correlated to the efficiency of the photothermal therapy and to the catalytic activity of GOx at each stage, enabling real-time activatable CDx.

Dihydroartemisinin attenuates pulmonary inflammation and fibrosis in rats by suppressing JAK2/STAT3 signaling.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has induced a worldwide pandemic since early 2020. COVID-19 causes pulmonary inflammation, secondary pulmonary fibrosis (PF); however, there are still no effective treatments for PF. The present study aimed to explore the inhibitory effect of dihydroartemisinin (DHA) on pulmonary inflammation and PF, and its molecular mechanism. Morphological changes and collagen deposition were analyzed using hematoxylin-eosin staining, Masson staining, and the hydroxyproline content. DHA attenuated early alveolar inflammation and later PF in a bleomycin-induced rat PF model, and inhibited the expression of interleukin (IL)-1ß, IL-6, tumor necrosis factor α (TNFα), and chemokine (C-C Motif) Ligand 3 (CCL3) in model rat serum. Further molecular analysis revealed that both pulmonary inflammation and PF were associated with increased transforming growth factor-ß1 (TGF-ß1), Janus activated kinase 2 (JAK2), and signal transducer and activator 3(STAT3) expression in the lung tissues of model rats. DHA reduced the inflammatory response and PF in the lungs by suppressing TGF-ß1, JAK2, phosphorylated (p)-JAK2, STAT3, and p-STAT3. Thus, DHA exerts therapeutic effects against bleomycin-induced pulmonary inflammation and PF by inhibiting JAK2-STAT3 activation. DHA inhibits alveolar inflammation, and attenuates lung injury and fibrosis, possibly representing a therapeutic candidate to treat PF associated with COVID-19.